Suppression of peripheral sympathetic activity underlies protease-activated receptor 2-mediated hypotension

Young Hwan Kim, Duck Sun Ahn, Ji Hyun Joeng, Seungsoo Chung

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω -conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω -CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

Original languageEnglish
Pages (from-to)489-495
Number of pages7
JournalKorean Journal of Physiology and Pharmacology
Volume18
Issue number6
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

Keywords

  • Hypotension
  • Mesenteric artery
  • N-type Ca channel
  • Peripheral sympathetic output
  • Protease-activated receptor 2

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